Caffeine is the most widely used psychoactive substance in the world and its use is increasing among children. Although considered safe, the majority of empirical data on the effects of caffeine have been collected in adults. Our previous studies, supported by a KO1 from NIDA, have demonstrated that caffeine has dose-dependent effects on physiological, mood, and energy intake in adolescents and that boys appear to be more sensitive to the effects of caffeine than girls. The following proposal describes a series of laboratory studies aimed at investigating the mechanisms underlying these gender differences, including pubertal development, steroid hormone concentrations, menstrual cycle phase, and adenosine receptor genotypes. These studies are important because they will provide much needed information on the effects of caffeine in children and adolescents as well as identify mechanisms that influence gender differences in response to caffeine and, perhaps, other drugs of abuse. PUBLIC HEALTH RELEVANCE: Our previous research suggests that the effects of caffeine in adolescents vary by gender. This proposal uses a multi-level, developmental approach to investigate the mechanisms underlying these gender differences in children and adolescents. The findings from these studies will help elucidate basic mechanisms that underlie gender differences in the response to caffeine and, perhaps other drugs of abuse and will improve our ability to identify factors that place individuals at higher risk for drug use and abuse.